Sodium Hydroxide → n-[4-(4-Amino-7-{(1e)-3-[(1h-benzimidazol-4-ylmethyl)amino]prop-1-enyl}thieno[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1h-indole-2-carboxamide

HRID 17220

Reaktionsgleichung

Reaktionsgleichung von HRID 17220
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](/[CH:32]=[CH:33]/[CH:34]=O)=[CH:4][N:3]=1.[CH:36]([C:38]1[N:39]=[CH:40][NH:41][CH:42]=1)=O.[BH4-].[Na+].[OH-].[Na+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(Cl)Cl.CO.C1(C)C=CC=CC=1>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](/[CH:32]=[CH:33]/[CH2:34][NH:1][CH2:2][C:7]2[C:42]3[N:41]=[CH:40][NH:39][C:38]=3[CH:36]=[CH:5][CH:6]=2)=[CH:4][N:3]=1

Komponenten

9

Edukt 4

HCID 14798Sodium HydroxideHCID 764281H-Imidazole-4-carbaldehydeHCID 4311764Sodium borohydrideHCID 18451050N-(4-{4-amino-7-[(1E)-3-oxoprop-1-enyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide

Produkt 1

HCID 68678346n-[4-(4-Amino-7-{(1e)-3-[(1h-benzimidazol-4-ylmethyl)amino]prop-1-enyl}thieno[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1h-indole-2-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11026Titanium isopropoxideKatalysatorHCID 887MethanolLösungsmittelHCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

In a round bottom flask was combined N-(4-{4-amino-7-[(1E)-3-oxoprop-1-enyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide (0.050 g, 0.104 mmol), 4-formylimidazole (0.0083 g, 0.086 mmol), and toluene (1.5 mL). The flask was flushed with nitrogen gas, followed by the addition of titanium (IV) isopropoxide (0.061 g, 0.215 mmol). The mixture was heated under a nitrogen atmosphere to 50° C. for 16 hours. The reaction mixture was cooled to room temperature and treated with methanol (1 mL) and sodium borohydride (0.010 g, 0.263 mmol). The resulting mixture was stirred for 12 hours at room temperature, followed by the addition of a 10% aqueous solution of sodium hydroxide (5 mL) and methylene chloride (5 mL). The mixture was filtered through an Empore™ cartridge, the solvents removed, and the product purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 Å, 25 cm; 5% acetonitrile—0.1M ammonium acetate isocratic for 5 minutes, then 5-100% acetonitrile—0.1M ammonium acetate over 30 min, 21 ml/min). The acetonitrile was removed and the aqueous solution was lyophilized to give the title compound as an off-white solid: 0.012 g (24%): LCMS (Conditions b): MH+=467.3, RT=2.35 minutes; 1H NMR (DMSO-d6, 400 MHz) δ 9.52 (s, 1 H), 7.99 (d, J=8.2 Hz, 1 H), 7.95 (s, 1 H), 7.70 (d, J=8.2 Hz, 1 H), 7.62 (s, 1 H), 7.59 (d, J=8.6 Hz, 1 H), 7.55 (s, 1 H), 7.35 (s, 1 H), 7.32 (d, J=8.6 Hz, 1 H), 7.21 (d, J=1.6 Hz, 1 H), 7.15 (dd, J=7.8 Hz, 7.0 Hz, 1 H), 7.08 (dd, J=7.8 Hz, 1.6 Hz, 1 H), 6.88 (s (br), 1 H), 6.67 (d, J=16.0 Hz, 1 H), 6.30 (td, J=16.4 Hz, 5.5 Hz, 1 H), 5.61 (s (br), 1 H), 4.04 (s, 3 H), 3.91 (s, 3 H), 3.67 (s, 2 H), 3.39 (d, J=5.5 Hz, 2 H), 2.78 (s, 15 H, acetate)

Aufarbeitung

  1. customIn a round bottom flask was combined
  2. customThe flask was flushed with nitrogen gas
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationThe mixture was filtered through an Empore™ cartridge
  5. customthe solvents removed
  6. customthe product purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 Å, 25 cm
  7. wait5% acetonitrile—0.1M ammonium acetate isocratic for 5 minutes
  8. wait5-100% acetonitrile—0.1M ammonium acetate over 30 min
  9. customThe acetonitrile was removed

Quellen und Nachweise

ORD-Eintrag
ord-d039e8ac5d15457589a973bfc91ec44c
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737160B2

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